The continuing objectives of this project are to characterize the functions of cells in the murine immune system and determine the mechanisms of action of these cells in the generation and regulation of antibody responses in tissue culture systems. These experiments focus on restrictions on macrophage-immune T cell interactions imposed by products of the A-A region of the H-2 gene complex. These restrictions have been demonstrated in macrophage-immune T cell interactions in responses to several protein antigens in addition to GAT. Moreover, antigen-specific suppressor T cells appear to dictate these restrictions, since the activity of immune helper T cells alone is not restricted. Lastly, subsets of T cells have been demonstrated in immune (responder X nonresponder) Fl mice which behave phenotypically as responder or nonresponder parental T cells with respect to antigen under Ir gene control and suggesting that functional allelic exclusion of Ir gene expression occurs in these T cell subsets. Experiments are in progress to: a) determine the mechanism(s) by which suppressor T cells dictate restrictions in helper T cell activity; b) positively select and eventually clone helper and suppressor T cell subsets from immune (responder X nonresponder) Fl mice; c) characteriz these cloned cells by cell surface and biochemical criteria; and, d) determine the interrelationships among these T cell subsets in the context of regulation of responses to antigens under Ir gene control. These studies should contribute to the understanding of fundamental mechanisms regulating generation and expression of immune responses by defining the interrelationships among the functions of helper and suppressor T cells, Ir genes and I region products which impose restrictions on macrophage-T cell interactions in antibody responses.